Bipolar disorders are frequent and disabling expression and unknown etiology. They are disorders of mood that can be manifested with a variety of symptoms including psychosis. Little is known about the causes of bipolar disorder but there is convincing evidence that both genetic and environmental factors play some role in the etiology of bipolar disorder. The mechanism is not known. Most investigators believe that bipolar disorders are etiologically heterogeneous and some believe that they may share some susceptibility genes with schizophrenia. The long term objective of this research is to localize and characterize genes of importance to Bipolar Disorders and to test the hypothesis that bipolar disorders share some genetically determined susceptibility with some form of schizophrenia. This will be achieved through molecular genetic approaches (i.e., linkage analysis and linkage disequilibrium studies using highly polymorphic microsatellite markers). Understanding the factors that contribute to the susceptibility of these disorders may benefit affected individuals and their relatives. Identification of the genes involved may provide new targets for the development of medications to ameliorate these disorders. It has been previously shown that genetically more homogenous populations provide certain advantages to the identification of susceptibility genes. In the effort described in this application, we aim to use the unique genetic structure of the Ashkenazi Jewish population to enable a genetic dissection of bipolar disorders. The specific aims of the proposal are as follows: 1) to recruit and evaluate a sample of 200 Ashkenazi Jewish families with at least two affected siblings and at least one parent willing to participate (Sib Pair Panel); 2) to recruit and evaluate an independent sample of 300 Ashkenazi Jewish patients who are diagnosed as having bipolar disorder and whose parents are willing to participate (Trio Panel). DNA will be isolated and lymphocytes will be isolated, frozen and stored for individuals in both the Sib Pair and Trio Panels ; 3) to complete a genome wide scan at a resolution of 10 cM using well-mapped highly polymorphic loci in the Sib-Pair Panel to detect new susceptibility loci; 4) to perform follow-up genotyping in the Trio Panel to create a denser map in the 10 regions identified in the genome scan to have the most evidence for a susceptibility gene for bipolar disorders; 5) to maintain contact with these families so follow-up may be possible in the future, and 6) to make this unique clinical resource available to other investigators pursuing this goal.